Giuseppe
Emeritus
[Source: PLoS Pathogens, full text: (LINK). Abtract, edited.]
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Cross-Reactive T Cells Are Involved in Rapid Clearance of 2009 Pandemic H1N1 Influenza Virus in Nonhuman Primates
by Jason T. Weinfurter, Kevin Brunner, Saverio V. Capuano, Chengjun Li, Karl W. Broman, Yoshihiro Kawaoka, Thomas C. Friedrich
In mouse models of influenza, T cells can confer broad protection against multiple viral subtypes when antibodies raised against a single subtype fail to do so. However, the role of T cells in protecting humans against influenza remains unclear. Here we employ a translational nonhuman primate model to show that cross-reactive T cell responses play an important role in early clearance of infection with 2009 pandemic H1N1 influenza virus (H1N1pdm). To ?prime? cellular immunity, we first infected 5 rhesus macaques with a seasonal human H1N1 isolate. These animals made detectable cellular and antibody responses against the seasonal H1N1 isolate but had no neutralizing antibodies against H1N1pdm. Four months later, we challenged the 5 ?primed? animals and 7 naive controls with H1N1pdm. In naive animals, CD8+ T cells with an activated phenotype (Ki-67+ CD38+) appeared in blood and lung 5?7 days post inoculation (p.i.) with H1N1pdm and reached peak magnitude 7?10 days p.i. In contrast, activated T cells were recruited to the lung as early as 2 days p.i. in ?primed? animals, and reached peak frequencies in blood and lung 4?7 days p.i. Interferon (IFN)-γ Elispot and intracellular cytokine staining assays showed that the virus-specific response peaked earlier and reached a higher magnitude in ?primed? animals than in naive animals. This response involved both CD4+ and CD8+ T cells. Strikingly, ?primed? animals cleared H1N1pdm infection significantly earlier from the upper and lower respiratory tract than the naive animals did, and before the appearance of H1N1pdm-specific neutralizing antibodies. Together, our results suggest that cross-reactive T cell responses can mediate early clearance of an antigenically novel influenza virus in primates. Vaccines capable of inducing such cross-reactive T cells may help protect humans against severe disease caused by newly emerging pandemic influenza viruses.
-by Jason T. Weinfurter, Kevin Brunner, Saverio V. Capuano, Chengjun Li, Karl W. Broman, Yoshihiro Kawaoka, Thomas C. Friedrich
In mouse models of influenza, T cells can confer broad protection against multiple viral subtypes when antibodies raised against a single subtype fail to do so. However, the role of T cells in protecting humans against influenza remains unclear. Here we employ a translational nonhuman primate model to show that cross-reactive T cell responses play an important role in early clearance of infection with 2009 pandemic H1N1 influenza virus (H1N1pdm). To ?prime? cellular immunity, we first infected 5 rhesus macaques with a seasonal human H1N1 isolate. These animals made detectable cellular and antibody responses against the seasonal H1N1 isolate but had no neutralizing antibodies against H1N1pdm. Four months later, we challenged the 5 ?primed? animals and 7 naive controls with H1N1pdm. In naive animals, CD8+ T cells with an activated phenotype (Ki-67+ CD38+) appeared in blood and lung 5?7 days post inoculation (p.i.) with H1N1pdm and reached peak magnitude 7?10 days p.i. In contrast, activated T cells were recruited to the lung as early as 2 days p.i. in ?primed? animals, and reached peak frequencies in blood and lung 4?7 days p.i. Interferon (IFN)-γ Elispot and intracellular cytokine staining assays showed that the virus-specific response peaked earlier and reached a higher magnitude in ?primed? animals than in naive animals. This response involved both CD4+ and CD8+ T cells. Strikingly, ?primed? animals cleared H1N1pdm infection significantly earlier from the upper and lower respiratory tract than the naive animals did, and before the appearance of H1N1pdm-specific neutralizing antibodies. Together, our results suggest that cross-reactive T cell responses can mediate early clearance of an antigenically novel influenza virus in primates. Vaccines capable of inducing such cross-reactive T cells may help protect humans against severe disease caused by newly emerging pandemic influenza viruses.
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